Caregiver coping strategies predict cognitive and functional decline in dementia: the Cache County Dementia Progression Study.

OBJECTIVES: Few longitudinal studies have studied the influence of the care environment on the clinical progression of dementia. We examined whether caregiver coping strategies predict dementia progression in a population-based sample. DESIGN: Longitudinal, prospective cohort study. SETTING: Cache County (Utah) population. PARTICIPANTS: A total of 226 persons with dementia, and their caregivers, were assessed semiannually for up to 6 years. MEASUREMENTS: Ways of Coping Checklist-Revised, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR). RESULTS: Mean (SD) age of dementia onset in persons with dementia was 82.11 (5.84) years and mean caregiver age was 67.41 (13.95) years. Mean (SD) follow-up was 1.65 (1.63) years from baseline. In univariate linear mixed-effects models, increasing use of problem-focused and counting blessings by caregivers was associated with slower patient worsening on the MMSE. Problem-focused coping, seeking social support, and wishful thinking were associated with slower Clinical Dementia Rating Scale sum of boxes (CDR-sb) worsening. Considering covariates, increasing use of problem-focused coping was associated with 0.70 points per year less worsening on the MMSE and 0.55 points per year less worsening on the CDR-sb. Compared with no use, the "regular" use of this strategy was associated with 2 points per year slower worsening on the MMSE and 1.65 points per year slower worsening on the CDR-sb. CONCLUSIONS: Caregiver coping strategies are associated with slower dementia progression. Developing interventions that target these strategies may benefit dementia patients.

Effects of general medical health on Alzheimer's progression: the Cache County Dementia Progression Study.

BACKGROUND: Several observational studies have suggested a link between health status and rate of decline among individuals with Alzheimer's disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression. METHODS: This was a case-only cohort study arising from a population-based longitudinal study of memory and aging, in Cache County, Utah. Participants comprised 335 individuals with incident AD followed for up to 11 years. Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the General Medical Health Rating (GMHR), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating - sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI). RESULTS: Health status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, and non-psychiatric medications) was associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: ß = -1.07 p = 0.01; CDR-sb: ß = 1.79 p < 0.001; NPI: ß = 4.57 p = 0.01). CONCLUSIONS: Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, it seems likely that there is a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted.

Effects of Food and Drug Administration-approved medications for Alzheimer's disease on clinical progression.

BACKGROUND: Observational studies suggest that cholinesterase inhibitors and/or memantine may delay clinical progression of Alzheimer's disease (AD) in 40% of individuals taking the medications. Given this response and existence of side effects, we sought to quantify medication use and benefits in a population-based study of incident AD cases. METHODS: The Cache County Dementia Progression Study enrolled and followed a cohort of 327 incident AD cases for a maximum of 9 years. Drug exposure was expressed using a persistency index (PI), calculated as total years of drug use divided by total years of observation. Linear mixed-effects models examined PI, and interactions with sex and apolipoprotein E (APOE) as predictors of clinical progression on the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. RESULTS: A total of 69 participants (21.1%) reported having ever used cholinesterase inhibitors or memantine. There was a strong three-way interaction between PI, sex, and time. Among women, a higher PI (i.e., greater duration of use) of cholinesterase inhibitors was associated with slower progression on the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes, particularly among those with an APOE ɛ4 allele. In contrast, higher PI was associated with faster progression in males. CONCLUSION: A low percentage of individuals with AD in the community are taking cholinesterase inhibitors or memantine. This study suggests that women, particularly those with an APOE ɛ4 allele, may benefit the most from these medications. With the newly approved increased dose of donepezil, it will be imperative to determine whether a higher dose is needed in men or whether other factors warrant consideration.

Progression of cognitive, functional, and neuropsychiatric symptom domains in a population cohort with Alzheimer dementia: the Cache County Dementia Progression study.

OBJECTIVES: Progression of Alzheimer dementia (AD) is highly variable. Most estimates derive from convenience samples from dementia clinics or research centers where there is substantial potential for survival bias and other distortions. In a population-based sample of incident AD cases, we examined progression of impairment in cognition, function, and neuropsychiatric symptoms, and the influence of selected variables on these domains. DESIGN: Longitudinal, prospective cohort study. SETTING: Cache County (Utah). PARTICIPANTS: Three hundred twenty-eight persons with a diagnosis of possible/probable AD. MEASUREMENTS: Mini-Mental State Exam (MMSE), Clinical Dementia Rating sum-of-boxes (CDR-sb), and Neuropsychiatric Inventory (NPI). RESULTS: Over a mean follow-up of 3.80 (range: 0.07-12.90) years, the mean (SD) annual rates of change were -1.53 (2.69) scale points on the MMSE, 1.44 (1.82) on the CDR-sb, and 2.55 (5.37) on the NPI. Among surviving participants, 30% to 58% progressed less than 1 point per year on these measures, even 5 to 7 years after dementia onset. Rates of change were correlated between MMSE and CDR-sb (r = -0.62, df = 201, p < 0.001) and between the CDR-sb and NPI (r = 0.20, df = 206, p < 0.004). Female subjects (LR χ = 8.7, df = 2, p = 0.013) and those with younger onset (likelihood ratio [LR] χ = 5.7, df = 2, p = 0.058) declined faster on the MMSE. Although one or more apolipoprotein E ε 4 alleles and ever use of FDA-approved antidementia medications were associated with initial MMSE scores, neither was related to the rate of progression in any domain. CONCLUSIONS: A significant proportion of persons with AD progresses slowly. The results underscore differences between population-based versus clinic-based samples and suggest ongoing need to identify factors that may slow the progression of AD.

Interpreting Mini-Mental State Examination Performance in Highly Proficient Bilingual Spanish-English and Asian Indian-English Speakers: Demographic Adjustments, Item Analyses, and Supplemental Measures.

Purpose: Performance on the Mini-Mental State Examination (MMSE), among the most widely used global screens of adult cognitive status, is affected by demographic variables including age, education, and ethnicity. This study extends prior research by examining the specific effects of bilingualism on MMSE performance. Method: Sixty independent community-dwelling monolingual and bilingual adults were recruited from eastern and western regions of the United States in this cross-sectional group study. Independent sample t tests were used to compare 2 bilingual groups (Spanish-English and Asian Indian-English) with matched monolingual speakers on the MMSE, demographically adjusted MMSE scores, MMSE item scores, and a nonverbal cognitive measure. Regression analyses were also performed to determine whether language proficiency predicted MMSE performance in both groups of bilingual speakers. Results: Group differences were evident on the MMSE, on demographically adjusted MMSE scores, and on a small subset of individual MMSE items. Scores on a standardized screen of language proficiency predicted a significant proportion of the variance in the MMSE scores of both bilingual groups. Conclusions: Bilingual speakers demonstrated distinct performance profiles on the MMSE. Results suggest that supplementing the MMSE with a language screen, administering a nonverbal measure, and/or evaluating item-based patterns of performance may assist with test interpretation for this population.

Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1.

Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer's disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time ß= 0.22, p = 0.017; mMNA by time2 ß= -0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (ß= 0.35, p <  0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention.

Predictors of dementia caregiver depressive symptoms in a population: the Cache County dementia progression study.

OBJECTIVES: Previous research has consistently reported elevated rates of depressive symptoms in dementia caregivers, but mostly with convenience samples. This study examined rates and correlates of depression at the baseline visit of a population sample of dementia caregivers (N = 256). METHOD: Using a modified version of Williams (Williams, I. C. [2005]. Emotional health of black and white dementia caregivers: A contextual examination. The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences, 60, P287-P295) ecological contextual model, we examined 5 contexts that have contributed to dementia caregiver depression. A series of linear regressions were performed to determine correlates of depression. RESULTS: Rates of depressive symptoms were lower than those reported in most convenience studies. We found fewer depressive symptoms in caregivers with higher levels of education and larger social support networks, fewer health problems, greater likelihood of using problem-focused coping, and less likelihood of wishful thinking and with fewer behavioral disturbances in the persons with dementia. DISCUSSION: These results suggest that depression may be less prevalent in populations of dementia caregivers than in clinic-based samples, but that the correlates of depression are similar for both population and convenience samples. Interventions targeting individuals with small support networks, emotion-focused coping styles, poorer health, low quality of life, and those caring for persons with higher numbers of behavioral problems need development and testing.

Interaction between vascular factors and the APOE ε4 allele in predicting rate of progression in Alzheimer's disease.

Vascular factors have been shown to affect the rate of Alzheimer's disease (AD) progression. However, the effect of the APOE ε4 allele on rate of progression has been ambiguous. Little research to date has examined an interaction between vascular factors and the APOE ε4 allele in predicting decline among AD patients. 216 participants with incident AD from a population of elderly persons in Cache County, Utah, were followed for a mean of 3.3 years and 4.2 follow-up visits. A history of vascular risk factors and conditions and anti-hypertensive use was assessed at the diagnostic visit. Linear mixed effects models tested interactions between the vascular factors, APOE ε4, and time as predictors of clinical progression on the Mini-Mental State Exam (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB). Multiple comparisons were corrected using the Holm-Bonferroni method. There was a 3-way interaction between stroke, APOE ε4 and time in predicting MMSE decline (LR χ² = 10.32, 2 df, p = 0.006). For the CDR-SB, there were 3-way interactions between the APOE ε4, time and either myocardial infarction (LR χ² = 17.83, 2 df, p = 0.0001) or stroke (LR χ² = 11.48, 2 df, p = 0.003. Results suggest a complex relationship between the APOE ε4 and vascular factors in predicting cognitive and functional progression. Among individuals with a history of stroke or myocardial infarction at baseline, progression of AD is influenced by APOE ε4 carrier status and varies by time after AD diagnosis.